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MLi-2, a Potent, Selective, and Centrally Active Compound for Exploring the Therapeutic Potential and Safety of LRRK2 Kinase Inhibition
TLDR
The suitability of MLi-2 as a compound to explore LRRK2 biology in cellular and animal models is demonstrated, with greater than 295-fold selectivity for over 300 kinases in addition to a diverse panel of receptors and ion channels. Expand
Six-hour window of opportunity for calpain inhibition in focal cerebral ischemia in rats.
TLDR
The data indicate that the therapeutic window of opportunity for calpain inhibition is at least 6 hours in a reversible focal cerebral ischemia model, suggesting that calpain activation may be an obligatory, downstream event in the ischemic cell death cascade. Expand
Benchmarking safety pharmacology regulatory packages and best practice.
TLDR
ICH S7A core battery studies are implemented by most of the responding companies with a clear trend of an enhanced submission of renal and GI studies and a diversity of approaches for conducting abuse liability studies, which primarily use the methods of self-administration and drug discrimination. Expand
Sensorimotor and cognitive consequences of middle cerebral artery occlusion in rats
TLDR
Rats subjected to either right proximal middle cerebral artery (MCA) occlusion or sham operation showed a general pattern of transient sensorimotor and reflex deficits, but with more persistent cognitive impairments, like that seen in humans following MCA infarcts. Expand
Protective effects of moderate hypothermia on behavioral deficits but not necrotic cavitation following cortical impact injury in the rat.
TLDR
Hypothermia, consistent with the reports of others, can produce significant behavioral protection following cortical impact injury that is not necessarily correlated with changes in focal cortical necrosis within the first 15 days following injury. Expand
Comparative Histopathologic Consequences of Photothrombotic Occlusion of the Distal Middle Cerebral Artery in Sprague‐Dawley and Wistar Rats
TLDR
This model has the advantages of necessitating only minimal surgery, allowing the dura to remain intact, and avoiding mechanical trauma to the brain surface, making the model suitable, for example, for replicate studies of pharmacotherapy. Expand
The organization of dorsal medullary projections to the central amygdaloid nucleus and parabrachial nuclei in the rabbit
TLDR
The results demonstrate that separate populations of neurons within the solitary complex of the rabbit project to the central amygdaloid and parabrachial nuclei and that the majority of these are located within the caudal two-thirds of the complex. Expand
Treatment window for hypothermia in brain injury.
TLDR
When hypothermia was administered immediately or 60 minutes after TBI, injured rats showed an improvement in functional outcome and a decrease in edema, and Delay of treatment by 90 or 120 minutes postinjury did not result in this neurological protection. Expand
MDL 101,002, a free radical spin trap, is efficacious in permanent and transient focal ischemia models.
TLDR
It is suggested that this novel cyclic nitrone spin trap affords effective neuroprotection and is useful for the treatment of ischemic stroke. Expand
Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats
TLDR
The data suggest that moderate intra-ischemic brain hypothermia provides long-lasting protection from behavioral deficits as well as neuronal injury following transient global ischemia. Expand
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